Bacteremia and meningitis following fiberoptic bronchoscopy.

Bacteremia and meningitis due to Streptococcus pneumoniae developed in a 52-year-old man 28 hours after an otherwise uncomplicated fiberoptic bronchoscopy. The patient responded to antimicrobial therapy and supportive care and later underwent pneumonectomy for carcinoma. This report reinforces previous observations that bacteremia may occasionally be associated with the performance of fiberoptic bronchoscopy.

Effect of aspartame plus monosodium L-glutamate ingestion on plasma and erythrocyte amino acid levels in normal adult subjects fed a high protein meal.

It has been suggested that aspartame addition to meals already containing large amounts of monosodium L-glutamate would result in an early rapid rise in plasma glutamate and/or aspartate concentrations and increase the potential for dicarboxylic amino acid-induced toxicity. Six normal adult subjects were fed hamburger and milk shake meals providing protein at 1 g/kg body weight in a randomized cross-over design. One meal had no additions while the other contained added monosodium L-glutamate and aspartame (each present at 34 mg/kg body weight). The addition of aspartame plus glutamate had little effect on either plasma or erythrocyte concentrations of glutamate or aspartate beyond those arising from the meal itself. Plasma phenylalanine concentrations were significantly higher (p less than 0.05, paired t test) after ingestion of meals containing aspartame plus glutamate reflecting the increased phenylalanine load.

Plasma glutamate concentrations in adult subjects ingesting monosodium L-glutamate in consomme.

The effect of MSG ingestion in consomme on the plasma glutamate concentration response was studied in normal adult subjects. In the first study nine subjects ingested three different consomme servings (providing 0, 25 and 50 mg/kg body weight MSG) in a Latin square design. Plasma glutamate concentrations were not significantly increased over baseline (3.69 +/- 1.08 mumol/dl) when no added MSG was present. However, mean peak plasma glutamate levels increased proportional to dose when MSG was added (10.2 +/- 2.00 and 17.0 +/- 8.06 mumol/dl at 25 and 50 mg/kg body weight respectively). Since six of the nine subjects in this study reported an idiosyncratic symptom response when tested with MSG at 150 mg/kg body weight, nine additional subjects were also studied. They ingested consomme providing MSG at 0 and 50 mg/kg body weight. No significant differences in plasma amino acid responses were noted between the two groups of subjects.

Modulating effect of Sustagen on plasma glutamate concentration in humans ingesting monosodium L-glutamate.

It has been suggested that monosodium L-glutamate (MSG) addition to meals would significantly increase plasma glutamate concentrations compared to values noted after ingestion of protein-bound glutamate. To test this hypothesis, plasma amino acid concentrations were measured in six normal adults ingesting a ready-to-feed liquid meal (Sustagen) containing added MSG at 0, 100, and 150 mg/kg body weight (Latin square design), and compared to plasma values noted after ingestion of 150 mg/kg body weight MSG in water. The mean (+/- SD) peak plasma glutamate concentrations after ingestion of meals providing 0, 100, and 150 mg/kg body weight MSG were 6.64 +/- 1.99, 11.2 +/- 4.89 and 10.8 +/- 3.10 mumol/dl, respectively. Erythrocyte glutamate concentrations were unchanged after each meal. Peak plasma glutamate concentrations after ingestion of meals with added MSG were similar to those noted in normal adults ingesting a similar quantity of protein-bound glutamate. In contrast, ingestion of MSG in water (150 mg/kg body weight) markedly increased the mean (+/- SD) peak plasma glutamate concentration to 71.8 +/- 35.7 mumol/dl. Similarly, the area under the plasma glutamate concentration-time-curve was significantly higher. MSG ingestion with meals results in lower plasma glutamate concentrations than ingestion of equivalent doses in water.

Effect of aspartame and sucrose loading in glutamate-susceptible subjects.

It has been postulated that individuals reporting an idiosyncratic symptom response after glutamate ingestion might also experience such symptoms after aspartame ingestion. Such sensitive subjects might have been missed in earlier studies of aspartame. In the present study, six subjects reporting various symptoms after glutamate ingestion, but not after placebo, were administered aspartame (34 mg/kg body weight) or sucrose (1 g/kg body weight) dissolved in orange juice in a randomized, cross-over, double-blind study. No subject reported symptoms typical of a glutamate response after either sucrose or aspartame loading. One subject reported slight nausea approximately 1.5 h after aspartame ingestion, but indicated that the symptoms were not those of a glutamate response. Plasma phenylalanine and aspartate levels were similar to those noted in normal subjects administered identical doses of aspartame. The data indicate no effect of aspartame loading in glutamate-susceptible subjects.

Effect of carbohydrate on plasma and erythrocyte glutamate levels in humans ingesting large doses of monosodium L-glutamate in water.

In previous studies, plasma glutamate concentration was lower when equivalent doses of monosodium L-glutamate (MSG) were given with a ready-to-feed liquid formula meal (Sustagen; 0.4 g protein, 1.1 g carbohydrate, 0.06 g fat, 6.6 kcal energy/kg body weight) rather than in water. This difference was suggested to reflect a carbohydrate effect on mucosal cell glutamate metabolism. To test this hypothesis, a large dose of monosodium L-glutamate (150 mg/kg body weight) dissolved in water, with or without added carbohydrate, was administered to eight healthy adult subjects. Carbohydrate was administered at 1.1 g/kg body weight in the form of partially hydrolyzed corn starch (Polycose). In the absence of carbohydrate, the mean (+/- SD) peak plasma glutamate concentration was 59.4 +/- 46.5 mumol/dl, and the incremental area under the plasma glutamate concentration time curve was 3391 +/- 2360 mumol/(dl x min). The addition of carbohydrate to the glutamate solution significantly decreased (p = 0.001) both the mean peak plasma glutamate concentration (7.18 +/- 3.48 mumol/dl) and the incremental area under the plasma glutamate concentration-time-curve (451 +/- 20.8 mumol/(dl x min). Erythrocyte glutamate and aspartate concentrations were not affected by glutamate loading in either test. Delayed gastric emptying did not account for the carbohydrate effect. Carbohydrate is postulated to serve as a pyruvate source for mucosal cells, facilitating the transamination of glutamate and its subsequent metabolism. This process would reduce the release of glutamate to the peripheral circulation.

Effect of sampling site on plasma amino acid concentrations of infants: effect of skin amino acids.

Plasma taurine, aspartate, threonine, serine, glycine, alanine, valine, leucine, tyrosine, phenylalanine, tryptophan, lysine, histidine, and ornithine concentrations are significantly greater (p less than 0.05, "Student's" t test) in blood samples obtained by conventional heel skin puncture techniques from 1-yr-old infants than values in venous plasma. Differences in plasma concentrations of taurine, aspartate, serine, glycine, and ornithine were particularly striking, with levels in plasma collected from the heel being 1.6 to 6.7 times higher than levels in venous plasma. These increased plasma amino acid concentrations were shown to result primarily from contamination of the plasma with amino acids present on the skin surface. Thorough washing and stimulation of blood flow to the heel by warming prior to skin puncture reduced observed differences. Plasma amino acid concentrations of blood samples obtained by conventional heel skin puncture procedures can be "normalized" to venous values through the use of data on the amino acid composition of heel skin washings.

Effect of sucrose ingestion on plasma glutamate concentrations in humans administered monosodium L-glutamate.

Plasma glutamate concentrations in human subjects are markedly lower when monosodium L-glutamate (MSG) is ingested in consomme with starch than when ingested in consomme alone. This study investigated whether sucrose had a similar effect. Six normal adult subjects (three male, three female) ingested two servings of beef consomme each providing 50 mg MSG/kg body weight in a randomized crossover design. One serving of consomme contained no added carbohydrate; the other provided 0.5 g sucrose/kg body weight. Ingestion of the consomme without sucrose significantly (p less than 0.05) increased the mean plasma glutamate concentration from baseline (4.44 +/- 0.97 mumol/dl) to a peak value of 18.1 +/- 6.99 mumol/dl 30 min after dosing. The area under the plasma glutamate concentration-time curve was 553 +/- 238 mumol/dl X min. When the consomme contained 0.5 g sucrose/kg body weight, both the mean peak plasma glutamate concentration (5.48 +/- 2.19 mumol/dl) and the area under the curve (105 +/- 46 mumol/dl X min) were significantly lower. These data confirm that metabolizable carbohydrate has a significant effect on plasma glutamate concentration response after MSG loading.

Plasma amino acid concentrations and amino acid ratios in normal adults and adults heterozygous for phenylketonuria ingesting a hamburger and milk shake meal.

Plasma amino acid concentrations were measured and selected amino acid ratios were calculated in 12 normal adults and 12 adults heterozygous for phenylketonuria (PKU) ingesting a hamburger and milk shake meal providing 1 g protein/kg body wt. Plasma concentrations of all amino acids increased significantly over baseline after meal ingestion in both groups, reaching the highest mean values 3-5 h after meal ingestion. Plasma phenylalanine concentrations were significantly higher in heterozygous than in normal subjects both before and at all times after meal ingestion. The absolute increase in plasma phenylalanine concentration over baseline and the area under the plasma phenylalanine concentration-time curve were approximately twice as large in heterozygous as in normal subjects. However, the molar ratio of the plasma phenylalanine concentration to the sum of the plasma concentrations of the other large neutral amino acids did not increase significantly over baseline, but rather decreased.

Visual and auditory cortical lesions following acquisition of an intensity discrimination in rats fail to disrupt cross-modal transfer.

The effect of visual or auditory decortication on cross-modal transfer of an intensity discrimination was examined in rats. Twenty animals were first trained under either visual-auditory (V-A) or auditory-visual (A-V) cross-modal transfer (CMT) in a shuttlebox using a shock avoidance pardigm. Prior to the second training session, five of the A-V animals received auditory ablations and five V-A animals received visual ablations. The other 10 animals served as controls and received sham operations. The results reveal that CMT occurred in both experimental groups following cortical ablations. It is possible that information regarding stimulus intensity was transferred from a cortical region used during the original training session to the cortex used in the second or retraining session, prior to surgery. Alternatively, it may be that some subcortical structure (e.g. the amygdala, superior colliculus, or reticular formation) may be involved in CMT of intensity.

Malignancy following treatment of rheumatoid arthritis with cyclophosphamide. Long-term case-control follow-up study.

A long-term retrospective case-control study was performed comparing 119 patients with rheumatoid arthritis treated with cyclophosphamide and 119 matched control patients with rheumatoid arthritis not treated with cyclophosphamide to determine the risk of subsequent malignancy. Thirty-seven malignancies were detected in 29 cyclophosphamide-treated patients, while 16 malignancies were found in 16 control patients (p less than 0.05) during a mean follow-up period of more than 11 years. Urinary bladder cancer (six cyclophosphamide-treated patients, no control patients) and skin cancer (eight cyclophosphamide-treated patients, no control patients) were identified as differing statistically between the groups, and hematologic malignancy (five cyclophosphamide-treated patients, one control patient) showed a similar trend. Survival analysis indicated that the rate of development of malignancy in the cyclophosphamide-treated patients was significantly greater than in the control patients at six years following drug initiation, and that this increased rate persisted even at 13 years (p less than 0.01). Of the many risk factors evaluated, mean total cyclophosphamide dose and duration and tobacco use were significantly increased in patients in whom cancer subsequently developed. These long-term complications must be considered seriously when cyclophosphamide or other cytotoxic drugs are initiated for the treatment of rheumatoid arthritis.

High doses of intravenous immunoglobulin G enhance Kupffer cell phagocytic function during the late phase of sepsis and endotoxemia in rats.

The effect of intravenous immunoglobuln G (ivIG) on the hepatic microvascular inflammatory response during the late phase of sepsis and endotoxemia in rats was studied by using in vivo microscopy. One hour after administration of a clinically relevant dose of ivIG (0.5 g/kg body weight, Sandoglobulin), rats were subjected to polymicrobial sepsis induced by cecal ligation and puncture (CLP) or were injected intravenously with lipopolysaccharide (LPS, 0.1 mg/kg body weight). Twenty-four hours after CLP or LPS, the number of leukocytes adhering to the sinusoidal wall was increased 11.0-fold in CLP-treated animals and 5.6-fold in LPS-treated animals, respectively, compared with the controls. Concomitantly, the numbers of swollen sinusoidal endothelial cells were increased 4.2-fold and 3.2-fold. The number of perfused sinusoids was decreased by 35% and by 24%. These responses were minimized by pretreatment with high doses of ivIG. Kupffer cell phagocytic activity in the periportal sinusoids in CLP-treated animals was decreased by 41%, whereas that in the centrilobular sinusoids in LPS-treated animals was increased by 72%. IvIG significantly elevated this activity in both CLP- and LPS-treated animals and the number of ED2-positive Kupffer cells in tissue sections. The results suggest that ivIG limits the hepatic microvascular inflammatory response during the late phase of sepsis and endotoxemia by affecting Kupffer cell function.

Effect of immunoglobulin G on the hepatic microvascular inflammatory response during sepsis.

The effects of intravenous immunoglobulin G (ivIG) on the hepatic microvascular inflammatory response to sepsis were studied in rats by in vivo microscopy. High doses of ivIG (300 mg/kg bw) (Sandoglobulin or rat IgG) significantly improved the 48 h survival of septic rats from 25-66% when ivIG was given before or immediately after cecal ligation and puncture. Circulating endotoxin also was significantly reduced. Eight hours after inducing sepsis, the average number of leukocytes adhering to the sinusoidal endothelium increased 15-fold and the average decrease in the number of perfused sinusoids was 22%. IvIG administration minimized these responses. In both septic and nonseptic animals, ivIG also reduced the phagocytic activity of Kupffer cells. The results suggest that high doses of ivIG not only reduce lethality but also limit hepatic microcirculatory dysfunction during sepsis by minimizing leukocyte-endothelial interactions that may be a result of reducing circulating endotoxin and modifying Kupffer cell function.

Effect of intravenous immunoglobulin G on the TNFalpha-mediated hepatic microvascular inflammatory response.

The effect of intravenous immunoglobulin G (ivIG) on the hepatic microvascular inflammatory response elicited by tumor necrosis factor alpha (TNFalpha) in rats was studied by means of in vivo microscopy and histological examination. One hour after the portal infusion of TNFalpha, the average number of leukocytes adhering to the sinusoidal endothelium was increased sevenfold, and the average number of the perfused sinusoids was decreased by 15% when compared with controls. Concomitantly, the expression of intercellular adhesion molecule-1 (ICAM-1) on the hepatic sinusoidal endothelium and that of the central vein was increased. The phagocytic activity of Kupffer cells in centrilobular sinusoids was increased by 54%, as were the number of ED2-positive Kupffer cells in tissue sections. Pretreatment with a clinically relevant high dose of ivIG (1 g/kg body weight, Sandoglobulin) minimized these responses by reducing leukocyte-endothelial interactions and Kupffer cell phagocytic function. The results suggest that high doses of ivIG limit the hepatic microvascular inflammatory response by inhibiting the action of the proinflammatory cytokine TNFalpha.

Plasma amino acid concentrations in normal adults ingesting aspartame and monosodium L-glutamate as part of a soup/beverage meal.

We tested the hypothesis that ingestion of monosodium L-glutamate with aspartame produces a marked increase in plasma glutamate and aspartate concentrations. Twelve normal adults (6 males, 6 females) ingested three different soup/beverage meals in a balanced Latin square design. One meal (A) provided no aspartame (APM) or monosodium L-glutamate (MSG); a second (B) provided 50 mg MSG/kg body weight; while the third (C) provided 50 mg MSG and 34 mg APM per kg body weight. Plasma glutamate (Glu) concentrations were not significantly affected by meal A but increased significantly after meals B and C (no significant difference between B and C). Plasma aspartate (Asp) concentrations were not significantly affected by meal A but increased significantly after meals B and C (values significantly higher after meal C than meal B). Plasma Glu + Asp concentrations were not significantly affected by meal A but increased significantly from a mean (+/- SD) baseline value of 5.64 +/- 2.62 mumol/dL to high mean values of 23.1 +/- 7.29 and 26.8 +/- 9.74 mumol/dL after ingestion of meals B and C, respectively (no significant difference between meals B and C). Similarly, the area under the plasma Glu + Asp concentration-time curve did not differ significantly between meals B and C (624 +/- 197 v 763 +/- 277 mumol/dL x min, respectively). Peak plasma Glu + Asp concentrations for each subject (ignoring time) were also examined. The mean peak plasma Glu + Asp concentrations were 7.39 +/- 2.77, 23.0 +/- 6.61, and 27.3 +/- 9.07 mumol/dL, respectively after meals A, B, and C.

Repeated ingestion of aspartame-sweetened beverage: effect on plasma amino acid concentrations in normal adults.

Aspartame (APM) is a dipeptide sweetener (L-aspartyl-L-phenylalanine methyl ester). It has been suggested that excessive use of the product might elevate plasma aspartate and phenylalanine concentrations. Eight normal adults (four male, four female) ingested three successive 12-oz servings of APM-sweetened beverage at two-hour intervals. The study was carried out in two parts in a randomized cross-over design. In one study the beverage was not sweetened. In the other, the beverage provided 10 mg APM/kg body weight per serving. Plasma amino acid concentrations were measured throughout the six-hour study period. The addition of APM to the beverage had no significant effect on plasma aspartate concentration. APM addition did increase plasma phenylalanine levels 1.64 to 2.05 mumol/dL above baseline values (5.09 +/- 0.82 mumol/dL) 30 to 45 minutes after each dose. However, plasma phenylalanine levels did not exceed normal postprandial values at any time. The data indicate ready metabolism of APM's amino acid content when administered at levels likely to be ingested by individuals who are heavy users of such beverages.

Repeated ingestion of aspartame-sweetened beverage: effect on plasma amino acid concentrations in individuals heterozygous for phenylketonuria.

It has been suggested that excessive use of aspartame (APM) (N-L-alpha-aspartyl-L-phenylalanine methyl ester) might grossly elevate plasma aspartate and phenylalanine concentrations in individuals heterozygous for phenylketonuria (PKUH). In study 1 six adult PKUH (three males; three females) ingested three successive 12-oz servings of beverage at 2-h intervals. The study was carried out in two parts in a randomized crossover design. In one arm the beverage was not sweetened. In the other the beverage provided 10 mg APM/kg body weight per serving. The addition of APM to the beverage did not significantly increase plasma aspartate concentration but did increase plasma phenylalanine levels 2.3 to 4.1 mumol/dL above baseline values 30 to 45 min after each dose. The high mean plasma phenylalanine level after repeated APM dosing (13.9 +/- 2.15 mumol/dL) was slightly, but not significantly, above the normal postprandial range for PKUH (12.6 +/- 2.11 mumol/dL). In study 2 six different adult PKUH ingested beverage providing 30 mg APM/kg body weight as a single bolus. The high mean plasma phenylalanine concentration and the phenylalanine to large neutral amino acid ratio were significantly higher when APM was ingested as a single bolus than when ingested as a divided dose.

Plasma phenylalanine levels in phenylketonuric heterozygous and normal adults administered aspartame at 34 mg/kg body weight.

Following administration of aspartame (34 mg/kg body wt) in orange juice, plasma concentrations of free amino acids were measured in 12 female subjects known to be heterozygous for phenylketonuria and 22 normal subjects (12 male, 10 female). No change in fasting plasma aspartate concentrations were noted after aspartame loading in either group. In normal male subjects, the mean (+/-S.D.) plasma phenylalanine concentration increased from a fasting value of 5.86 +/- 1.25 mumol/dl. Plasma phenylalanine levels in normal female subjects increased from a mean fasting concentration of 4.83 +/- 0.84 mumol/dl to a men peak value of 8.95 +/- 1.49 mumol/dl suggesting a more rapid absorption, metabolism, and/or clearance of phenylalanine by females. In female heterozygous subjects, the mean peak plasma phenylalanine concentration was significantly higher than in normal females. Plasma phenylalanine values increased from a mean fasting value of 5.92 +/- 1.51 mumol/dl to a mean peak value of 15.1 +/- 4.76 mumol/dl. Similarly, the area under the plasma phenylalanine concentration-time curve was significantly greater in heterozygous female subjects (21.36 +/- 5.10 IU) than in normal female subjects (10.84 +/- 2.32 IU). However, peak plasma phenylalanine levels were well below those associated with toxic effects in all cases.

Digit replantation in infants and young children: determinants of survival.

Thirty-three children under 34 months of age with 41 digits amputated over a 15-year period were reviewed. There were 3 primary amputations, 6 composite grafts, and 32 replantations. Twenty-one variables were evaluated for their influence on 4-week digit survival. The overall survival rate of 32 replanted digits was 69 percent. Favorable uncontrollable variables were clean-cut injury and body weight greater than 11 kg. Favorable controllable variables included more than one vein repaired, bone shortening, interosseous bone fixation, and vein grafting of arteries or veins. Forty-one percent of children required a blood transfusion. Children with trauma to more than one digit were most likely to be transfused (p < 0.05). The combination of prompt digit reperfusion after successful arterial repair and at least one successful venous anastomosis resulted in a 95 percent digit survival rate, significantly higher than the 0 percent survival of digits lacking one or the other of these features.

Fasciocutaneous island flap based on the medial plantar artery: clinical applications for leg, ankle, and forefoot.

Soft-tissue deficits over the plantar forefoot, plantar heel, tendo calcaneus, and lower leg are often impossible to cover with a simple skin graft. The previously developed medial plantar fasciocutaneous island flap has been adapted to cover soft-tissue defects over these areas. This fasciocutaneous flap based on the medial plantar neurovascular bundle is capable of providing sensate and structurally similar local tissue. Application of this fasciocutaneous island flap is demonstrated in 12 clinical cases. Successful soft-tissue cover was achieved on the plantar calcaneus (four patients), tendo calcaneus (four patients), lower leg (two patients), and plantar forefoot (two patients). Follow-up ranged from 6 months to 5 years. All flaps were viable at follow-up. Protective sensation was present in 11 of 12 flaps evaluated at 6 months. In addition, all 11 patients were able to ambulate in normal footwear. The medial plantar island flap seems to be more durable than a skin graft, and the donor site on the non-weight-bearing instep is well tolerated. This study demonstrates that the medial plantar fasciocutaneous island flap should be considered as another valuable tool in reconstructive efforts directed at the plantar forefoot, plantar heel, posterior ankle, and lower leg.